BDDE is the most commonly used homobifunctional epoxide compound. BDDE may react with e.g. amines, acids, hydroxyls and sulfhydryl groups to produce secondary amines, ester, ether or thioether bonds, respectively. BDDE is a cross linking agent used e.g. for preparing amylose, xylan and hydroxyethyl-cellulose; to cross-link polyethylenimine; to cross-link glycosaminoglycans such as hyaluronic acid into hydrogels: for the activation of soluble dextran polymers; and amine or hydroxyl containing bis-epoxy supports are reacted with BDDE to form particles containing terminal epoxide group for immobilization reactions.
Hyaluronic acid consists of a linear unbranched polysaccharide of disaccharide subunits. The subunit is a pair of pyranose sugars, D-Glucuronic acid and N-Acetyl D-Glucosamine, linked by beta 1-3 and beta 1-4 glycosidic bonds. HA can make intra-molecular and inter-molecular interactions by hydrogen bonding. These hydrogen bonds are responsible for the folding of the polysaccharide. Due to its numerous negative charges, HA can retain large amounts of water and acts therefore as a space filler, lubricant and osmotic buffer. However, the poor mechanical properties, rapid degradation and clearance in vivo of soluble hyaluronic acid limit its use as a biomaterial. To improve the mechanical properties and to increase the resistance to degradation by hyaluronidases, HA is chemically modified or cross-linked to form hydrogels. This polysaccharide can e.g. be crosslinked by ether or ester bonds with a diepoxy linker such as BDDE to produce a hydrogel that is composed of a three-dimensional network.
HA is primarily degraded by three different mechanisms: enzymatic degradation, free radical degradation and thermal degradation. Enzymatic degradation is mediated by a large class of enzymes, including endo-glucosidases that breaks down glycosaminoglycans, such as HA, chondroitin or chondroitin sulfate, into smaller fragments which subsequently join the natural elimination process in the body.